SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats—natural reservoirs of sarbecoviruses...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500467X |
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| author | Risako Gen Amin Addetia Daniel Asarnow Young-Jun Park Joel Quispe Matthew C. Chan Jack T. Brown Jimin Lee Melody G. Campbell Christopher P. Lapointe David Veesler |
| author_facet | Risako Gen Amin Addetia Daniel Asarnow Young-Jun Park Joel Quispe Matthew C. Chan Jack T. Brown Jimin Lee Melody G. Campbell Christopher P. Lapointe David Veesler |
| author_sort | Risako Gen |
| collection | DOAJ |
| description | Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats—natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover. |
| format | Article |
| id | doaj-art-efbb4d93bd1940908091401b78dd53e6 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-efbb4d93bd1940908091401b78dd53e62025-08-20T01:49:23ZengElsevierCell Reports2211-12472025-05-0144511569610.1016/j.celrep.2025.115696SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammalsRisako Gen0Amin Addetia1Daniel Asarnow2Young-Jun Park3Joel Quispe4Matthew C. Chan5Jack T. Brown6Jimin Lee7Melody G. Campbell8Christopher P. Lapointe9David Veesler10Department of Biochemistry, University of Washington, Seattle, WA 98195, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USADivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USADivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USADepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA; Corresponding authorSummary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats—natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover.http://www.sciencedirect.com/science/article/pii/S221112472500467XCP: Microbiology |
| spellingShingle | Risako Gen Amin Addetia Daniel Asarnow Young-Jun Park Joel Quispe Matthew C. Chan Jack T. Brown Jimin Lee Melody G. Campbell Christopher P. Lapointe David Veesler SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals Cell Reports CP: Microbiology |
| title | SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals |
| title_full | SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals |
| title_fullStr | SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals |
| title_full_unstemmed | SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals |
| title_short | SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals |
| title_sort | sars cov 2 nsp1 mediates broad inhibition of translation in mammals |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500467X |
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